Lead is a known neurotoxic metal, and child externalizing behavior (aggression, ADHD, and oppositional disorder) has been identified as a risk factor for adolescent delinquency and later adult violence. There is preliminary evidence that even at sub- clinical lead exposure levels, children experence negative cognitive and behavioral outcomes. However, it is still unclear whether such effects are sustained or how the pathogenesis of the effect of sub-clinical lead exposure is shaped. Based on the evidence from our preliminary analyses in a longitudinal cohort study, we propose to study the mediating mechanisms by which exposure to lead during the preschool years contribute to externalizing behavior in early adolescence. Lead exposure is hypothesized to give rise to two related symptoms, cognitive impairment (low IQ, reduced P300 event- related potentials, poor school performance) and emotion dysregulation (low vagal tone, low arousal, and low stress reactivity) which in turn form the mechanistic pathway to childhood externalizing behavior. This new R01 builds on the PI's current NIEHS-funded K award and unique data from an on-going large prospective cohort study. The initial epidemiological sample consisted of 1,650 3-5 year-old Chinese boys and girls whose blood lead levels were obtained in 2004, and their IQ test scores and behavioral measures were assessed at age 6 years. We propose to add new neurocognitive and emotion measures in addition to repeating measures of blood lead, IQ, behavior, school performance, and psychosocial risk factors during preadolescent years (estimate N =1,200). Structural equation modeling will be used to test the main effect, interactive and mediating effects of early lead exposure on later externalizing behavior. The interdisciplinary research team has decades of experience in studying lead exposure, child behavior problems, psychophysiology, and child mental health. Findings have potential theoretical and clinical implications for understanding the symptoms of neurocognitive and emotional effects of lead exposure on children's externalizing behavior. By integrating neuroscience assessment tools with epidemiology and toxicology, this study could potentially inform strategies for lowing current CDC-defined safe lead levels, and reduce the likelihood of neurocognitive deficits and behavior problems. Ultimately it will potentially minimize the impact of negative environmental exposures on children's mental health, thus improving their subsequent well-being over the life-course. PUBLIC HEALTH RELEVANCE: Understanding the neurobiological basis of lead exposure on children's externalizing behavior will be significant to future attempts to tackle two important global public health issues: lead exposure and children externalizing behavior, ultimately helping to improve the quality life of the individual and the family unit.